This application proposes to develop molecularly designed peptide nanostructures that can trigger differentiation of progenitor cells and mineralization in physiological media with features that mimic enamel or bone matrices. The proposed research is based on the hypothesis that regeneration of enamel and bone can be triggered by templates designed at the nanoscale to present biological signals and induce biomimetic mineralization. Using in vitro assays, we will investigate how these biomimetic mineralization templates affect matrix synthesis by ameloblasts and osteoprogenitor cells, and also test their performance in embryonic tooth culture and in vivo bone repair models. This research will guide the development of synthetic, versatile, nanostructured templates that can be used for hard tissue (enamel or bone) regeneration and repair without the need for autologous or autogenic tissue transplantation. The proposed program's specific aims include: development of peptide amphiphiles that will self-assemble in physiological fluids and trigger biomimetic mineralization of enamel- or bone-like matrices, testing of these nanofiber systems in vitro with osteoprogenitor and ameloblast cells using mineralization, protein and gene expression assays, and using patterned substrates or scaffolds of peptide amphiphile nanofibers for in vitro and in vivo regeneration of dental and bone tissues in murine models. The proposed research program is a collaborative effort of four investigators specializing in self-assembly/materials chemistry, dental tissue biology and orthopedic surgery, whose interests intersect on the focused application of nanoscience and nanotechnology to biomedical research.